title: Interactions of platelets, macrophages, and lipoproteins in hypercholesterolemia: antiatherogenic effects of HMG-CoA reductase inhibitor therapy.
abstract: To assess the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on plasma cholesterol concentrations and on platelet aggregation, lovastatin or fluvastatin, 40 mg daily, was given to hypercholesterolemic patients. After 24 weeks, plasma low-density lipoprotein (LDL) cholesterol concentrations were reduced by 37% after lovastatin therapy and 29% after fluvastatin therapy. The platelet cholesterol/phospholipid ratio was reduced by 33% and 26%, respectively. Platelet aggregation was significantly reduced by 12-15% (p < 0.01) after 4 weeks of therapy with either agent. Lovastatin or fluvastatin therapy reduced platelet aggregation through an in vivo hypocholesterolemic action on the platelet cholesterol content and also through a direct effect on platelet function, as a result of drug binding to the platelets. We also studied the effect of these HMG-CoA reductase inhibitors on LDL susceptibility to oxidation. LDL oxidation (induced by copper ions) was reduced by 31% after lovastatin therapy and by 37% after fluvastatin therapy. The inhibitory effect of HMG-CoA reductase inhibitors on LDL oxidation involved their stimulatory effect on the removal of LDL from the circulation and a direct binding effect of the drugs to the lipoprotein. Because HMG-CoA reductase inhibitors can inhibit platelet aggregation, macrophage foam cell formation, and LDL oxidation, major contributors to atherogenesis, the use of these drugs can significantly attenuate the atherosclerotic process.
authors.affiliation: Lipid Research Laboratory, Rambam Medical Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Aviram
authors.forename: O
authors.initials: O
authors.lastname: Hussein
authors.forename: M
authors.initials: M
authors.lastname: Rosenblat
authors.forename: S
authors.initials: S
authors.lastname: Schlezinger
authors.forename: T
authors.initials: T
authors.lastname: Hayek
authors.forename: S
authors.initials: S
authors.lastname: Keidar
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D002450:Cell Communication; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000032:analysis / Q000187:drug effects; D008148:Lovastatin / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D010975:Platelet Aggregation Inhibitors; D000077340:Fluvastatin; D008148:Lovastatin